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NCT02477839 Clinical Trial

Efficacy and Safety of Lacosamide as Adjunctive Therapy in Subjects ≥1 Month to <4 Years With Partial-onset Seizures

Epilepsy With Partial-onset Seizures Clinical Trial

Official title:
A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study to Investigate the Efficacy and Safety of Lacosamide as Adjunctive Therapy in Subjects With Epilepsy >=1 Month to <4 Years of Age With Partial-Onset Seizures

Clinical Trial Details — Status: Completed

Administrative data
NCT number NCT02477839
Other study ID # SP0967
Secondary ID 2013-000717-20
Status Completed
Phase Phase 3
First received
Last updated
Start date June 5, 2015
Est. completion date May 28, 2020

Study information
Verified date June 2021
Source UCB Pharma
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this trial is to assess the efficacy, safety and tolerability of lacosamide administered as add-on therapy with 1 to 3 anti-seizure medications. This trial is for children aged 1 month to less than 4 years with epilepsy who currently have uncontrolled partial-onset seizures.

Description:

The trial consists of a 7-day Baseline Period, a 20-day Titration Period, a 7-day Maintenance Period, and a 12-day Transition Period for subjects who complete the study and choose to enter the extension study. Subjects who will not enter the extension study will continue after the Maintenance Period with a 16-day Taper Period followed by a 30-day Safety Follow-Up Period. The Taper Period and Safety Follow-Up are also applicable for subjects not eligible for continuation and therefore ending the study earlier. If subjects meet the eligibility criteria, they will be randomized to receive either lacosamide 8 mg/kg/day to 12 mg/kg/day, or placebo during the Maintenance Phase. The dose of lacosamide will be titrated from 4 mg/kg/day at study start to maximum of 12 mg/kg/day at 4-day intervals of 1-2 mg/kg/day. All subjects who complete the 20-day Titration Period will enter the 7-day Maintenance Period. No dose adjustment is allowed during the Maintenance Phase. The Treatment Phase is defined as the combined Titration and Maintenance Phases.

Recruitment information / eligibility
Status Completed
Enrollment 255
Est. completion date May 28, 2020
Est. primary completion date May 28, 2020
Accepts healthy volunteers No
Gender All
Age group 1 Month to 47 Months
Eligibility Inclusion Criteria: - Subject is male or female from >=1 month (ie, 4 weeks after full term [37 weeks gestational age]) to <4 years of age - Subject has a diagnosis of epilepsy with partial-onset seizures. The results of >=1 prior EEG and >=1 magnetic resonance imaging/computerized tomography scan should be consistent with this diagnosis - Subject weighs >=4 kg to <30 kg at Visit 1 - Subject has experienced >=2 partial-onset seizures with or without secondary generalization during each consecutive 7-day period during the 2 weeks prior to Visit 1 - Subject has >=2 partial-onset seizures with or without secondary generalization during the End-of-Baseline video-EEG. Electrographic seizures are defined as recognizable ictal patterns on an EEG involving >=2 contiguous electrodes. The seizures are initiated as a unilateral or strongly asymmetric abnormal epileptiform discharge lasting a total of >10 seconds - Subject is on a stable (concurrently or sequentially) dosage regimen of 1 to 3 AEDs. The dosage regimen of concomitant AED therapy must be kept constant for a period of >=2 weeks prior to Visit 1. A stable daily dosage regimen of a concomitant benzodiazepine (BZD) will be considered as a concomitant AED - Vagus nerve stimulation (VNS) is allowed and will not be counted as a concomitant AED. The VNS device must have been implanted for >=6 months prior to Visit 1; device settings must be kept stable for >=2 weeks prior to Visit 1 and kept stable during the Baseline, Treatment, and Transition Periods. Use of the VNS device magnet is allowed - Subject is an acceptable candidate for venipuncture Exclusion Criteria: - Subject has experienced febrile seizures exclusively. The occurrence of febrile seizures in addition to partial-onset seizures is not exclusionary - Subject is on a ketogenic diet that has either changed within the 4 weeks prior to Visit 1 or is expected to change during the study - Subject has creatinine clearance <30 mL/minute - Subject has a clinically relevant ECG abnormality, in the opinion of the investigator (eg, second or third degree heart block at rest or a corrected QT interval [QTc] >=450 ms) - Subject has a hemodynamically significant congenital heart disease - Subject has an arrhythmic heart condition requiring medical therapy - Subject has a known history of severe anaphylactic reaction secondary to medication intake or serious blood dyscrasias - Subject has nonepileptic events that could be confused with seizures. Subjects may be included if epileptic events can be clearly distinguished and the frequency meets the study inclusion criteria - Subject has a current diagnosis of Lennox-Gastaut syndrome, epilepsia partialis continua, primary generalized epilepsy, Dravet Syndrome, or seizures that are not of partial-onset origin - Subject has a history of generalized convulsive status epilepticus <=2 months prior to Screening (Visit 1) - Subject has been treated with felbamate and has experienced any serious toxicity issues (defined as liver failure, aplastic anemia) with this treatment. Subjects treated with felbamate for <12 months are excluded. Subjects treated with felbamate for >=12 months prior to Visit 1 and who have not experienced serious toxicity issues are eligible - Subject has an acute or subacutely progressive central nervous system disease. Subject has epilepsy secondary to a progressing cerebral disease or any other progressively neurodegenerative disease (malignant brain tumor or Rasmussen Syndrome) - Subject has a known cardiac sodium channelopathy, such as Brugada syndrome

Study Design

Related Conditions & MeSH terms

Intervention

Drug:
• Lacosamide
Active Substance: Lacosamide Pharmaceutical Form: Syrup Concentration: 10 mg/mL Route of Administration: oral
Other:
• Placebo
Active Substance: Placebo Pharmaceutical Form: Syrup Concentration: N/A Route of Administration: oral

Locations
Country Name City State
Argentina Sp0967 142 Córdoba
Brazil Sp0967 158 Passo Fundo
Brazil Sp0967 152 Porto Alegre
Brazil Sp0967 150 São Paulo
Brazil Sp0967 154 São Paulo
Bulgaria Sp0967 310 Plovdiv
China Sp0967 530 Beijing
China Sp0967 535 Changchun
China Sp0967 532 Chongqing
China Sp0967 536 Nanchang
China Sp0967 531 Shanghai
China Sp0967 537 Shenzhen
Croatia Sp0967 613 Osijek
Croatia Sp0967 610 Rijeka
Croatia Sp0967 612 Zagreb
Czechia Sp0967 320 Ostrava-Poruba
France Sp0967 349 Marseille
France Sp0967 346 Rennes
France Sp0967 344 Strasbourg
Georgia Sp0967 620 Tbilisi
Georgia Sp0967 621 Tbilisi
Georgia Sp0967 622 Tbilisi
Georgia Sp0967 623 Tbilisi
Greece Sp0967 542 Athens
Hungary Sp0967 361 Budapest
Hungary Sp0967 362 Budapest
Hungary Sp0967 363 Budapest
Hungary Sp0967 364 Budapest
Hungary Sp0967 368 Budapest
Israel Sp0967 374 Petah tikva
Italy Sp0967 397 Genova
Italy Sp0967 398 Messina
Italy Sp0967 381 Milano
Italy Sp0967 700 Napoli
Italy Sp0967 383 Roma
Italy Sp0967 395 Roma
Korea, Republic of Sp0967 212 Seoul
Korea, Republic of Sp0967 215 Seoul
Mexico Sp0967 694 Aguascalientes
Mexico Sp0967 561 Chihuahua
Mexico Sp0967 569 Culiacán
Mexico Sp0967 693 Culiacán
Mexico Sp0967 563 Guadalajara
Mexico Sp0967 564 Mexico
Mexico Sp0967 568 Monterrey
Mexico Sp0967 692 Monterrey
Moldova, Republic of Sp0967 650 Chisinau
Philippines Sp0967 720 Cebu
Philippines Sp0967 724 Cebu
Philippines Sp0967 721 Manila
Philippines Sp0967 723 Manila
Philippines Sp0967 727 Quezon City
Poland Sp0967 422 Kraków
Portugal Sp0967 750 Lisbon
Romania Sp0967 581 Bucuresti
Romania Sp0967 582 Iasi
Romania Sp0967 573 Sibiu
Romania Sp0967 577 Timisoara
Russian Federation Sp0967 454 Kemerovo
Russian Federation Sp0967 456 Nizhny Novgorod
Russian Federation Sp0967 452 Novosibirsk
Russian Federation Sp0967 453 Omsk
Russian Federation Sp0967 455 Perm
Russian Federation Sp0967 730 Smolensk
Russian Federation Sp0967 458 Tomsk
Russian Federation Sp0967 459 Ulyanovsk
Russian Federation Sp0967 450 Yekaterinburg
Serbia Sp0967 461 Belgrade
Serbia Sp0967 464 Belgrade
Serbia Sp0967 463 Novi Sad
Slovakia Sp0967 474 Bratislava
Taiwan Sp0967 224 Taipei
Thailand Sp0967 237 Bangkok
Thailand Sp0967 235 Pathum Wan
Ukraine Sp0967 609 Dnipro
Ukraine Sp0967 602 Dnipropetrovs'k
Ukraine Sp0967 681 Ivano-Frankivs'k
Ukraine Sp0967 600 Kiev
Ukraine Sp0967 606 Kiev
Ukraine Sp0967 682 Uzhgorod
Ukraine Sp0967 603 Vinnytsia
United States Sp0967 638 Birmingham Alabama
United States Sp0967 129 Dallas Texas
United States Sp0967 115 Henderson Nevada
United States Sp0967 120 Lebanon New Hampshire
United States Sp0967 630 San Antonio Texas
United States Sp0967 643 San Antonio Texas
United States Sp0967 117 Tampa Florida

Sponsors (1)
Lead Sponsor Collaborator
UCB BIOSCIENCES, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Bulgaria,  China,  Croatia,  Czechia,  France,  Georgia,  Greece,  Hungary,  Israel,  Italy,  Korea, Republic of,  Mexico,  Moldova, Republic of,  Philippines,  Poland,  Portugal,  Romania,  Russian Federation,  Serbia,  Slovakia,  Taiwan,  Thailand,  Ukraine, 

Outcome
Type Measure Description Time frame Safety issue
Primary Change in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures From End-of-Baseline (EOB) Period Video-EEG to End-of-Maintenance (EOM) Period Video-EEG The change in ADF of electrographic partial-onset seizures as measured on the End-of-Maintenance Period video-electroencephalogram (EEG) compared to the End-of-Baseline Period video-EEG.
Seizure frequency was analyzed using an analysis of covariance (ANCOVA) with terms for treatment, pooled randomized age stratum, pooled center, and Baseline seizure ADF. Seizure ADF was log transformed using the transformation of ln(X+1), where X is the seizure ADF. Baseline seizure ADF was log transformed.
Least squares means were based on log-transformed data of the full ANCOVA model.		 End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)
Primary Participant Withdrawals Due to Adverse Events (AEs) During the Study An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. An AE could, therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study medication. From the Baseline Period (Day -7) to the End of Study Visit (up to 93 days)
Primary Percentage of Participants With Adverse Events Reported Spontaneously by the Participant's Parent(s) and/or Legal Representative(s)/Caregiver(s) (in Accordance With Local Regulation) or Observed by the Investigator An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. An AE could, therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study medication. From the Baseline Period (Day -7) to the End of Study Visit (up to 93 days)
Secondary Absolute Change in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures From End-of-Baseline (EOB) Period Video-EEG to End-of-Maintenance (EOM) Period Video-EEG The absolute change in ADF of electrographic partial-onset seizures as measured on the End-of-Maintenance Period video-EEG compared to the End-of-Baseline Period video-EEG. End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)
Secondary Percent Change in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures From End-of-Baseline (EOB) Period Video-EEG to End-of-Maintenance (EOM) Period Video-EEG The percent change in ADF of electrographic partial-onset seizures as measured on the End-of-Maintenance Period video-EEG compared to the End-of-Baseline Period video-EEG. End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)
Secondary Percentage of Participants Who Achieved 'Seizure-free' Status From All Seizure Types During the End-of-Maintenance (EOM) Period Video-EEG A study participant was considered seizure-free from all seizures if the End-of-Maintenance (EOM) Period video-EEG had zero seizures reported from all seizure types (not just partial-onset seizures (POS)). During the End-of-Maintenance Period (Day 24 to Day 27)
Secondary Percentage of Participants Who Achieved 'Seizure-free' Status From Partial-onset Seizure Types Only During the End-of-Maintenance (EOM) Period Video-EEG A study participant was considered seizure free from partial-onset seizures (POS) if the End-of-Maintenance (EOM) Period video-EEG had zero POS reported. During the End-of-Maintenance Period (Day 24 to Day 27)
Secondary Percentage of Participants Experiencing a >=25% to <50% Reduction in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures From End-of-Baseline (EOB) Period Video-EEG to End-of-Maintenance (EOM) Period Video-EEG A =25% to <50% response was defined as =25% to <50% reduction in ADF of electrographic partial-onset seizures (POS) from the End-of-Baseline (EOB) video-EEG to the End-of-Maintenance (EOM) video-EEG. End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)
Secondary Percentage of Participants Experiencing a 50% to 75% Reduction in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures From End-of-Baseline (EOB) Period Video-EEG to End-of-Maintenance (EOM) Period Video-EEG A =50% to =75% response was defined as =50% to =75% reduction in ADF of electrographic partial-onset seizures (POS) from the End-of-Baseline (EOB) video-EEG to the End-of-Maintenance (EOM) video-EEG. End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)
Secondary Percentage of Participants Experiencing a >75% Reduction in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures From End-of-Baseline (EOB) Period Video-EEG to End-of-Maintenance (EOM) Period Video-EEG A >75% response was defined as >75% reduction in ADF of electrographic partial-onset seizures (POS) from the End-of-Baseline (EOB) video-EEG to the End-of-Maintenance (EOM) video-EEG. End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)
Secondary Percentage of Participants Experiencing no Change in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures (Between <25% Reduction and <25% Increase) From EOB Period Video-EEG to EOM Period Video-EEG No change was defined as between <25% reduction and <25% increase in ADF of electrographic partial-onset seizures (POS) from the End-of-Baseline (EOB) video-EEG to the End-of-Maintenance (EOM) video-EEG. End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)
Secondary Percentage of Participants Experiencing an Increase in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures of >=25% From End-of-Baseline (EOB) Period Video-EEG to End-of-Maintenance (EOM) Period Video-EEG An increase was defined as =25% increase in ADF of electrographic partial-onset seizures (POS) from the End-of-Baseline (EOB) video-EEG to the End-of-Maintenance (EOM) video-EEG. End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)